Divicine induces endothelial cells injury and its potential mechanism

Abstract

Divicine is an active pyrimidine aglycone, generated from vicine by the enzyme β-glucosidase upon ingestion of fava beans. In this study, we investigated the effect of divicine on cultured human umbilical vein endothelial cells (HUVECs) and explored the potential mechanisms. Incubation HUVECs with 18.5–85.1 μM divicine resulted in a concentration and time dependent decrease of cell viability, followed by decrease of cellular reduced glutathione, as well as increase of reactive oxygen species (ROS), malondialdehyde (MDA), and labile iron pool. Transmission electron microscopy confirmed that the divicine treated HUVECs’ mitochondria had shrunk. Importantly, the administration of desferrioxamine, an iron chelator, to the divicine treated HUVECs significantly reduced iron overload and cell death and decreased cellular ROS and MDA. These results demonstrated that divicine could cause damaging of endothelial cells, and ferroptosis might be involved in divicine induced HUVECs injury, reminding long term ingestion of fava beans might be harmful to vascular system, especially for those suffering from glucose 6-phosphate dehydrogenase deficiency.